PAH-DNA adducts, cigarette smoking, GST polymorphisms, and breast cancer risk

Environ Health Perspect. 2009 Apr;117(4):552-8. doi: 10.1289/ehp.0800119. Epub 2008 Dec 10.

Abstract

Background: Polycyclic aromatic hydrocarbons (PAHs) may increase breast cancer risk, and the association may be modified by inherited differences in deactivation of PAH intermediates by glutathione S-transferases (GSTs). Few breast cancer studies have investigated the joint effects of multiple GSTs and a PAH biomarker.

Objective: We estimated the breast cancer risk associated with multiple polymorphisms in the GST gene (GSTA1, GSTM1, GSTP1, and GSTT1) and the interaction with PAH-DNA adducts and cigarette smoking.

Methods: We conducted unconditional logistic regression using data from a population-based sample of women (cases/controls, respectively): GST polymorphisms were genotyped using polymerase chain reaction and matrix-assisted laser desorption/ionization time-of-flight assays (n = 926 of 916), PAH-DNA adduct blood levels were measured by competitive enzyme-linked immunosorbent assay (n = 873 of 941), and smoking status was assessed by in-person questionnaires (n = 943 of 973).

Results: Odds ratios for joint effects on breast cancer risk among women with at least three variant alleles were 1.56 [95% confidence interval (CI), 1.13-2.16] for detectable PAH-DNA adducts and 0.93 (95% CI, 0.56-1.56) for no detectable adducts; corresponding odds ratios for three or more variants were 1.18 (95% CI, 0.82-1.69) for ever smokers and 1.44 (95% CI, 0.97-2.14) for never smokers. Neither interaction was statistically significant (p = 0.43 and 0.62, respectively).

Conclusion: We found little statistical evidence that PAHs interacted with GSTT1, GSTM1, GSTP1, and GSTA1 polymorphisms to further increase breast cancer risk.

Keywords: GST; Long Island; PAH-DNA adducts; breast cancer; smoking.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / genetics
  • DNA Adducts / analysis*
  • Female
  • Glutathione Transferase / genetics*
  • Humans
  • Middle Aged
  • Polycyclic Aromatic Hydrocarbons / analysis*
  • Polymorphism, Genetic*
  • Risk Assessment / methods
  • Risk Factors
  • Smoking*

Substances

  • DNA Adducts
  • Polycyclic Aromatic Hydrocarbons
  • polycyclic aromatic hydrocarbons-DNA adduct
  • Glutathione Transferase